Patterns of prescription opioid use before total hip and knee replacement among US Medicare enrollees.

OBJECTIVE: To examine patterns of prescription opioid use before total joint replacement (TJR) and factors associated with continuous use of opioids before TJR. DESIGN: We conducted an observational cohort study among Medicare enrollees aged ≥65 years who underwent TJR between 2010 and 2014. Preoperative opioid use was defined as having any opioid prescription in the 12-month period before TJR. Patients who had an opioid prescription every month for a 12-month period were defined as continuous users. We examined patients' demographics, pain-related conditions, medication use, other comorbidities, healthcare utilization and their association with use of opioids before TJR. RESULTS: A total of 473,781 patients underwent TJR:,155,516 THR and 318,265 TKR. Among the total cohort, 60.2% patients had any use of opioids and of those, 12.4% used opioids at least once a month continuously over the 12-month baseline period. Correlates of continuous opioid use included African American race (OR = 2.14, 95% confidence intervals (CI) = 2.01-2.28, compared to White patients), history of drug abuse (OR = 5.18, 95% CI = 3.95-6.79) and back pain (OR = 2.32, 95% CI = 2.24-2.39). CONCLUSIONS: In this large cohort of patients undergoing TJR, over 60% ever used opioids and 12.4% of them continuously used opioids in the 12-month prior to surgery. Utilization of opioids became more frequent and high-dosed near the surgery. History of drug abuse, back pain, and African American race were strongly associated with continuous use of opioids preoperatively. Further research is needed to determine short-term and long-term risks of preoperative use of opioids in TJR patients and to optimize pre- and post-TJR pain management of patients with arthritis.

Patterns and predictors of persistent opioid use following hip or knee arthroplasty.

OBJECTIVE: The relationship between arthroplasty and long-term opioid use in patients with knee or hip osteoarthritis is not well studied. We examined the prevalence, patterns and predictors of persistent opioid use after hip or knee arthroplasty. METHOD: Using claims data (2004-2013) from a US commercial health plan, we identified adults who underwent hip or knee arthroplasty and filled ≥1 opioid prescription within 30 days after the surgery. We defined persistent opioid users as patients who filled ≥1 opioid prescription every month during the 1-year postoperative period based on group-based trajectory models. Multivariable logistic regression was used to determine preoperative predictors of persistent opioid use after surgery. RESULTS: We identified 57,545 patients who underwent hip or knee arthroplasty. The mean ± SD age was 61.5 ± 7.8 years and 87.1% had any opioid use preoperatively. Overall, 7.6% persistently used opioids after the surgery. Among patients who used opioids in 80% of the time for ≥4 months preoperatively (n = 3023), 72.1% became persistent users. In multivariable analysis, knee arthroplasty vs hip, a longer hospitalization stay, discharge to a rehabilitation facility, preoperative opioid use (e.g., a longer duration and greater dosage and frequency), a higher comorbidity score, back pain, rheumatoid arthritis, fibromyalgia, migraine and smoking, and benzodiazepine use at baseline were strong predictors for persistent opioid use (C-statistic = 0.917). CONCLUSION: Over 7% of patients persistently used opioids in the year after hip or knee arthroplasty. Given the adverse health effects of persistent opioid use, strategies need to be developed to prevent persistent opioid use after this common surgery.

Percentage of signal intensity loss for characterisation of focal liver lesions in patients with chronic liver disease using ferucarbotran-enhanced MRI.

The purpose of this study was to determine the percentage of signal intensity loss (PSIL) threshold for the characterisation of focal liver lesions among patients with chronic liver disease. 55 nodules in 49 patients with chronic liver disease who underwent ferucarbotran-enhanced MR studies were included. Among the 49 patients, 40 had liver cirrhosis and 9 had chronic hepatitis. 8 haemangiomas, 3 focal nodular hyperplasia, 9 dysplastic nodules and 12 well, 19 moderately and 4 poorly differentiated hepatocellular carcinomas (HCCs) were revealed. The PSIL, signal-to-noise ratio and contrast-to-noise ratio of each lesion type were calculated. The diagnostic performance of PSIL on ferucarbotran-enhanced T(2) weighted images (PSIL(T2WI)) and T(2) weighted fat-suppression images (PSIL(FS-T2WI)) that characterised hepatic tumours was compared with receiver operating characteristic (ROC) analysis. Using ROC analysis, the diagnostic performance of PSIL(FS-T2WI) was superior to that of PSIL(T2WI) (p = 0.01). The mean PSIL(FS-T2WI) of the benign lesions was significantly higher than that of HCC (p<0.001), and the mean PSIL(FS-T2WI) of well-differentiated HCC was significantly higher than that of moderately/poorly differentiated HCCs (p = 0.001). With a PSIL(FS-T2WI) threshold of 40% in lesions characterising ferucarbotran-enhanced FS-T2WI, the sensitivity, specificity, accuracy, positive predictive value and negative predictive value were 88.6%, 95%, 90.9%, 96.9% and 82.6%, respectively. In conclusion, with ferucarbotran-enhanced FS-T2WI, a PSIL(FS-T2WI) threshold of 40% for characterising focal liver nodules among patients with chronic liver disease is recommended. It is useful for distinguishing HCC from benign nodules.

A blinded randomized controlled trial of motivational interviewing to improve adherence with osteoporosis medications: design of the OPTIMA trial.

UNLABELLED: We have designed an innovative randomized controlled trial for improving adherence with osteoporosis medications. Recruitment and randomization have been successful. Also, the counseling intervention has been well accepted by subjects randomized to this treatment arm. INTRODUCTION: While many effective treatments exist for osteoporosis, most people do not adhere to such treatments long term. No proven interventions exist to improve osteoporosis medication adherence. We report here on the design and initial enrollment in an innovative randomized controlled trial aimed at improving adherence to osteoporosis treatments. METHODS: The trial represents a collaboration between academic researchers and a state-run pharmacy benefits program for low-income older adults. Beneficiaries beginning treatment with a medication for osteoporosis are targeted for recruitment. We randomize consenting individuals to receive 12 months of mailed education (control arm) or an intervention consisting of one-on-one telephone-based counseling and the mailed education. Motivational interviewing forms the basis for the counseling program which is delivered by seven trained and supervised health counselors over ten telephone calls. The counseling sessions include scripted dialog and open-ended questions about medication adherence and its barriers, as well as structured questions. The primary end point of the trial is medication adherence measured over the 12-month intervention period. Secondary end points include fractures, nursing home admissions, health care resource utilization, and mortality. RESULTS: During the first 7 months of recruitment, we have screened 3,638 potentially eligible subjects. After an initial mailing, 1,115 (30.6%) opted out of telephone recruitment and 1,019 (28.0%) could not be successfully contacted. Of the remaining, 879 (24.2%) consented to participate and were randomized. Women comprise over 90% of all groups; mean ages range from 77 to 80 years old, and the majority in all groups was white. The distribution of osteoporosis medications was comparable across groups and the median number of different prescription drugs used in the prior year was eight to ten. CONCLUSIONS: We have developed a novel intervention for improving osteoporosis medication adherence. The intervention is currently being tested in a large-scale randomized controlled trial. If successful, the intervention may represent a useful model for improving adherence to other chronic treatments.

Detection of hepatocellular carcinoma by ferucarbotran-enhanced magnetic resonance imaging: the efficacy of accumulation phase fat-suppressed T1-weighted imaging.

AIM: To evaluate the effectiveness of accumulation phase, fat-suppressed, T1-weighted imaging (FS-T1WI) when detecting hepatocellular carcinoma (HCC) by ferucarbotran-enhanced magnetic resonance imaging (MRI). MATERIALS AND METHODS: Thirty patients who underwent ferucarbotran-enhanced MRI, which resulted in 35 confirmed HCCs, were included in this prospective study. Two image sets were prepared and two radiologists independently reviewed these in two reading sessions; set A was without contrast-enhanced accumulation phase FS-T1WI and set B included contrast-enhanced accumulation phase FS-T1WI. All HCCs had been confirmed by operation (n=4), by biopsy (n=28), and by follow-up study for at least 1 year (n=3). RESULTS: The contrast-to-noise ratio significantly increased from -1.2+/-7.5 to 12.7+/-7.3 with contrast-enhanced accumulation phase FS-T1WI, but was only slightly increased from 12.2+/-10.3 to 15.5+/-12.2 with contrast-enhanced T2WI (p<0.001). The signal-to-noise ratio (SNR) was decreased with T1WI and T2WI for liver parenchyma. With T2WI, the SNR for HCCs was decreased; however, it was slightly increased with T1WI (p<0.001). Overall, 29 HCCs were detected using set A, and 35 nodules were identified using set B, which included the contrast-enhanced accumulation phase FS-T1WI. Thus, the detection rate significantly increased using post-contrast medium accumulation phase FS-T1WI (p<0.05). CONCLUSION: Due to the improved CNR with the post-contrast medium accumulation phase FS-T1WI, which helped to increase HCC detection, accumulation phase FS-T1WI is recommended as one of the routine protocols for inclusion in HCC detection.

Imaging well-differentiated hepatocellular carcinoma with dynamic triple-phase helical computed tomography.

To investigate the imaging appearance of well-differentiated hepatocellular carcinoma (HCC) on dynamic CT, a total of 38 histopathologically proven well-differentiated HCC were included in a retrospective study. We reviewed the contrast-enhanced dynamic CT of all 38 tumours for attenuation of each tumour in unenhanced scan, arterial-dominant and delayed portal venous phases. Our results showed that dynamic CT identified 26 (68.4%) out of the 38 lesions. The remaining 12 lesions were isodense compared with surrounding liver parenchyma in each dynamic CT phase. There was no statistically significant difference between the mean size of tumours detected by dynamic CT and that of tumours not detected by dynamic CT (p = 0.1). Of a total of 38 tumours, most were isodense (n = 19) or hypodense (n = 16) in unenhanced scan, mostly hyperdense (n = 18) or isodense (n = 15) in arterial-dominant phase and mostly isodense (n = 22) or hypodense (n = 15) in delayed portal venous phase. Enhancement of tumour was observed in 19 (50.0%) of 38 lesions. In conclusion, the ability of dynamic CT to detect well-differentiated HCC is poor, and negative CT findings cannot exclude the presence of well-differentiated HCC, especially if there is well-grounded clinical suspicion for HCC.

An integrated treatment delivery system for CSRS and CSRT and clinical applications.

An integrated treatment delivery system for conformal stereotactic radiosurgery (CSRS) and radiotherapy (CSRT) has been developed through a collaboration involving Siemens Medical Systems, Inc., Tyco/Radionics, Inc., and The University of Texas M. D. Anderson Cancer Center. The system consists of a 6-MV linear accelerator (LINAC) equipped with a Tyco/Radionics miniature multileaf collimator (mMLC). For the conventional SRS treatment, the circular collimator housing can be attached to the opening window of the mMLC. The treatment delivery system is integrated with a radiotherapy treatment planning system and a record-and-verify system. The purpose of this study is to report the characteristics, performance, benefits, and the clinical applications of this delivery system. The technical specifications of the LINAC and mMLC were tested, and all the specifications were met. The 80% to 20% penumbral width for each mMLC leaf is approximately 3 mm and is nearly independent of the off-axis positions of a leaf. The maximum interleaf leakage is 1.4% (1.1% on average) and the maximum intra-leaf leakage is 1.0% (0.9% on average). The leaf position precision is better than 0.5 mm for all the leaves. The integration of the SRS/SRT treatment planning system, mMLC, and LINAC has been evaluated successfully for transferring the patient treatment data file through radiotherapy treatment planning system to the patient information and treatment record-and-verify server and the mMLC controller. Subsequently, the auto-sequential treatment delivery for SRS, CSRS/CSRT, and the step-and-shoot intensity-modulated radiotherapy has also been tested successfully. The accuracy of dose delivery was evaluated for a 2-cm spherical target in a Radiological Physics Center SRS head phantom with GAFChromic films and TLD. Five non-coplanar arcs, using a 2-cm diameter circular collimator, were used for this simulation treatment. The accuracy to aim the center of the spherical target was within 0.5 mm and the deviation of dose delivery to the isocenter of the target was within 2% of the calculated dose. For the irregularly shaped tumor, a tissue-equivalent head phantom was used to evaluate the accuracy of dose delivery for using either geometric conformal treatment or IMRT. The accuracy of dose delivery to the isocenter was within 2% and 3% of the calculated dose, respectively. From October 26, 1999 to September 30, 2002, we treated over 400 SRS patients and 70 SRT patients. Four representative cases are presented to illustrate the capabilities of this dedicated unit in performing conventional SRS, CSRS, and CSRT. For all the cases, the geometric conformal-plan dose distributions showed a high degree of conformity to the target shape. The degree of conformity can be evaluated using the target-volume-ratio (TVR). Our preferred TVR values for highly conformed dose distributions range from 1.6 to 2.0. The patient setup reproducibility for the Gill-Thomas-Cosman (GTC) noninvasive head frame ranges from 0.5 to 1 mm, and the head and neck noninvasive frame is within 2 mm. The integrated treatment delivery system offers excellent conformation for complicated planning target volumes with the stereotactic setup approach, ensuring that dose delivery can be achieved within the specified accuracy. In addition, the treatment time is comparable with that of single isocenter multiple-arc treatments.

[ Measuring and assessing the quality of life of patients with pulmonary tuberculosis].

OBJECTIVE: To measure and assess the quality of life (QoL) of patients with pulmonary tuberculosis. METHOD: QoL of 228 patients with pulmonary tuberculosis and 228 healty controls were marked by MOS SF-36, QLI and KPS scales, and single and multiple stepwise regression analysis were made to evaluate factors affecting QoL. RESULT: The average total mark of SF-36, marks of physical functioning, role-physical, mental health, role-emotional, social functioning, vitality, bodily pain and general health were respectively 57 +/- 17, 65 +/- 28, 22 +/- 32, 61 +/- 20, 30 +/- 36, 54 +/- 27, 56 +/- 21, 65 +/- 24 and 53 +/- 15 in the pulmonary tuberculosis group, while 77 +/- 8, 84 +/- 23, 81 +/- 34, 75 +/- 18, 81 +/- 33, 83 +/- 23, 61 +/- 21, 75 +/- 24 and 72 +/- 20 in the controls. Statistically significant differences were found between the two groups (all P values < 0.01). The average marks of QLI and KPS were 7.4 +/- 2.0 and 77 +/- 17 respectively in the pulmonary tuberculosis group, and significant differences were also found comparing with the controls (9.6 +/- 0.8, 97 +/- 9) (P < 0.01). There were statistically significant correlation among the total mark of SF-36 and the marks of the above 8 subdividions in patients with pulmonary tuberculosis. The correlation coefficients between marks of SF-36 and QLI, KPS were 0.7841, 0.8931 respectively (P < 0.001). The factors affecting the marks of SF-36 of the patients were focus size of infection, counts of white blood cells, complications, elevated ALT and duration of disease. CONCLUSION: The SF-36 scale is suitable for measurement of QoL of patients with pulmonary tuberculosis. The QoL of patients with pulmonary tuberculosis declines. The main factors affecting the QoL of the patients are focus size of infection, counts of white blood cells, complications, elevated ALT and duration of disease.

MM3(96) parameterization for camptothecin analogs: an ab initio and molecular mechanics study.

Torsional parameters for MM3(96) were derived for the missing atom types present in the natural product camptothecin (CPT). Potential energy curves were calculated via ab initio calculations on representative compounds for dihedral angles containing these missing parameters. Gaussian 92 at the restricted Hartree-Fock level of theory using the standard 6-31G** and 4-31G** basis sets, was used for all the quantum-mechanics calculations. Missing MM3 torsional terms were obtained by optimizing the V1, V2 and V3 parameters such that MM3 could reproduce the ab initio torsional profile. MM3 calculated molecular structures that compare well with the ab initio results. Using the newly developed parameters, conformational analyses and QSAR studies of camptothecin analogs were undertaken. MM3 predicts two distinct 'boatlike' conformations for the alpha-hydroxy lactone moiety. The low-energy lactone conformation predicted by MM3 is in general agreement with reported X-ray crystal structures of CPT iodoacetate and 7-ethyl-10-(4-piperidino)piperidinylcarbonyloxy CPT HCl as well as the ab initio structure of a CPT-like alpha-hydroxy lactone.

Antimutagenic effect of Maillard browning products obtained from amino acids and sugars.

The antimutagenic effects of Maillard reaction products (MRPs) prepared by heating three sugars (fructose, glucose and xylose) and four amino acids (arginine, glycine, lysine and tryptophan) at 100 degrees C for 10 hr was evaluated in the Salmonella/microsome assay. The highest extent of browning was found in the MRPs of sugars-lysine and xylose-amino acids. The MRPs of xylose-amino acids showed stronger antioxidative activity and reducing power than did the other combinations. No mutagenicity or toxicity in Salmonella typhimurium TA98 was observed with any of the MRPs in the presence of S-9. Most MRPs, especially those of sugars-tryptophan and xylose-amino acids, strongly inhibited the mutagenicity of 2-amino-3-methylimidazo(4,5-f)quinoline (IQ), 3-amino-1,4-dimethyl-5H-pyridol-(4,3-b)indole (Trp-P-1) and 2-amino-6-methyldipyrido(1,2-a:3',2'-d)imidazole (Glu-P-1) in the presence of S-9. However, the MRPs of fructose-glycine and fructose-arginine increased the mutagenicity of Trp-P-1. The antimutagenic effect of the MRPs was well correlated with their antioxidative activity and reducing power. The mutagenicity of benzo[a]pyrene was moderately inhibited by most MRPs, but was increased by the MRP of glucose-arginine. Aflatoxin B1 mutagenicity was increased greatly by all the MRPs except that of xylose-tryptophan. The findings suggested that MRPs might have a bifunctional property of co-mutagenicity and antimutagenicity in certain cases.

The dopaminergic moiety of the ergots: a controversial topic studied with molecular mechanics.

Conformational analyses of the side chain of model compounds of the in vivo active dopamine receptor agonist 4-[2-(di-n-propylamino)ethyl]indole (DPAI) were performed with molecular mechanics calculations. The results from these calculations, together with the possibility of meta hydroxylation of indoles in vivo, led to the proposal of fitting 6-hydroxy-4-[2-(di-n-propylamino)ethyl]indole (6-OH-DPAI), (S)-5-hydroxy-N,N-dialkyl-6,7,8,9-tetrahydro-3H-benzo[e]indol-8-ylami nes and (S)-5-hydroxy-2-(dialkylamino)tetralins in a common concept, considering both stereochemistry and hydrogen-bond function in such an overlap. This study emphasizes the importance of considering both conformational analysis and the possibilities of metabolic activation when performing structure-activity studies based on flexible compounds and in vivo data. The answer to the question as to which part of the ergot molecule is responsible for its dopaminergic effect is thus ambiguous. It is possible that the pyrrolylethylamine moiety of the ergots contributes to both in vitro and in vivo effects, and that their 13-OH metabolites contribute, possibly significantly, to their in vivo effects.

Conformational analysis of 2-aminoindans and 2-(aminomethyl)indans in relation to their central dopaminergic effects and a dynamic dopamine receptor concept.

Conformational analyses on differently substituted 2-aminoindans of significant pharmacological interest were carried out by the molecular mechanics method (MM2). An X-ray structure of (R)-4-methoxy-2-aminoindan has shown the ammonium nitrogen [-)-D-tartaric acid salt) in an axial position. From comparison with other, highly potent, centrally acting dopamine (DA) receptor agonists, it can be predicted that the active enantiomer (R)-4-hydroxy-2-(di-n-propylamino)indan should have its nitrogen atom in an equatorial position. This places it close to the aromatic ring plane, which is one of several prerequisites for potent DA receptor agonism. MM2 correctly calculates (R)-4-methoxy-2-aminoindan and (R)-4-hydroxy-2-(dialkylamino)indan to be more stable in the N-axial and N-equatorial conformations, respectively. Conformational analysis of the dimethyl model compound of the moderately potent dopaminergic phenylpropylamine analogue 4-hydroxy-2-[(di-n-propylamino)methyl]indan was also carried out, in order to see if any conformations of this compound satisfy the requirements for dopaminergic agonism. Two such stable conformations were found.